241st ENMC international workshop: Towards a European unifying lab for Kennedy's disease. 15–17th February, 2019 Hoofddorp, The Netherlands

Abstract

(M. Pennuto). 1 Members of the KD Consortium are listed under Participants at the end of this report. the presentations and discussions that took place during the workshop, which range from disease mechanisms, biomarker discovery, plans for an EU Registry for KD as well as an update on ongoing clinical trials. In addition, a dedicated session on the patient's perspective was presented. Kenneth Fischbeck opened the meeting with an overview of the disease. Kennedy's Disease (KD) also referred to as SBMA is a progressive X-linked neuromuscular disease characterized by bulbar and extremity muscle weakness, atrophy, and fasciculations. Affected males may show signs of androgen insensitivity, such as breast enlargement and reduced fertility. SBMA is caused by expansions of a CAG repeat in the androgen receptor (AR) gene. The disease typically presents in adult males with slowly progressive, relatively symmetrical, lower motor neuron weakness, perioral fasciculations, elevated creatine kinase, and decreased sensory potential amplitudes [1]. Common, but not invariable, manifestations are gynecomastia and a family history consistent with X-linked inheritance. Other non-neuromuscular features include Brugada syndrome [2] , urinary retention [3] , non-alcoholic fatty liver [4] , and fatigue. Primary degeneration of both motor neurons and muscle occurs in SBMA; there are clinical features of denervation and loss of motor neurons in the spinal cord and brainstem, and also increased creatine kinase and histological evidence of muscle fiber degeneration. The disease phenotype can be partially rescued in mouse models with molecular correction in either muscle or the central nervous system [5-7] .

Molecular pathogenesis of spinal bulbar muscular atrophy (Kennedy's disease) and avenues for treatment

“…The insights gained in studying cellular and animal models of SBMA are yielding therapeutic targets that can proceed to clinical investigation. Evaluation of candidate therapeutic options in SBMA patients is dependent on appropriate biomarkers to gauge therapeutic efficacy [26]. One of the strategies that has emerged for quantifying disease severity and progression is MRI imaging of limb muscles.…”